1. Field of the Invention
The present invention relates to the determination of the ionic strength or specific gravity of a test sample. More particularly, it relates to a composition, test device and method for determining the ionic strength or specific gravity of an aqueous test sample.
The determination of the specific gravity of a liquid has application in numerous arts. Thus, such unrelated disciplines as brewing, urinalysis, water purification, preparation of drinking water aboard a ship at sea, etc. all involve the measurement of specific gravity. Needless to say, a quick, facile method for determining this property would greatly enhance the state of many scientific arts, including any technology where rapid, accurate determination of specific gravity would be beneficial. Thus, for example, if a medical laboratory technician could accurately measure the specific gravity of a urine sample in a matter of seconds, not only would the rapid results aid the physician in diagnosis, but also laboratory efficiency would increase to a degree where many more analyses could be performed than were heretofore possible.
Although the present invention lends itself to a vast range of applications, for purposes of clarity this discussion will be couched largely in terms of the determination of the ionic strength or specific gravity of urine. Applications to other disciplines will become apparent from an understanding of how this invention relates to urinalysis.
The determination of urine specific gravity is of considerable value in the understanding and clinical management of electrolyte disturbances. Hence, complete urinalysis should, and usually does, include a specific gravity determination. Generally, such a determination would include the measurement of specific gravity directly with a suitable device, but equally useful is the measurement of some related property, such as osmolality or ionic strength, which can then be referred back to corresponding specific gravity values.
Specific gravity is a dimensionless term and relates, in the case of a solution, to the ratio of the weight of a certain volume of the solution to that of an equal volume of water at the same temperature. For solutions, such as urine, specific gravity is related to the number, density, ionic charge, and weight of the various species of dissolved solutes.
2. Description of the Prior Art
Prior art methods for determining specific gravity utilize hydrometers, urinometers, pycnometers, gravimeters, refractometers, and the like. Although these prior art procedures are satisfactorily sensitive in most cases, they all involve fragile, bulky instruments which must be constantly cleaned, maintained, and calibrated in order to continuously assure their reliability. In addition, there are many inconveniences associated with the mechanics of using these instruments. There may be a difficulty in reading the meniscus. Froth or bubbles on the liquid surface may interfere with the reading. There is a tendency for urinometers to adhere to the sides of the vessel containing the liquid sample. In the case of urine, the sample quantity is frequently inadequate for accommodating one of the aforementioned devices.
A recent breakthrough in which all of the above disadvantages have been virtually eliminated, and which affords rapid osmolality (ergo, specific gravity) determination, is disclosed in U.S. Pat. No. 4,015,462, assigned to the present assignee. This patent describes an invention in which a carrier matrix is incorporated with osmotically fragile microcapsules, the walls of which are composed of a semi-permeable membrane material. Encapsulated inside the walls is a solution containing a coloring substance. When the capsules are in contact with a solution having a lower osmolality than that within the capsules, an osmotic gradient occurs across the capsule walls in the direction of the lower osmolality, thereby increasing the hydrostatic pressure within the capsules, thus causing them to swell and, ultimately, to rupture, releasing their colored contents. The amount of color formed from this phenomenon is a function of the specific gravity of the solution.
It can be seen from the foregoing that besides the numerous devices which measure specific gravity directly, it is also possible to measure specific gravity using an indirect means such as the osmolality of a solution. Yet another way of estimating specific gravity without measuring it directly involves a determination which is proportional to the ionic strength of a solution. Such an approach is utilized by the present invention. It is well known that the specific gravity of an aqueous system is greatly affected by the presence of charged species. Thus, in the case of ionic solutions, it is possible to closely approximate the specific gravity of the respective solutions via measurements proportional to their ionic strengths and referring those measurements to a precalibrated reference system.
The term "ionic strength" refers to the mathematical relationship between the number of different kinds of ionic species in a particular solution and their respective charges. Thus, ionic strength .mu. is represented mathematically by the formula EQU .mu.=1/2.SIGMA.c.sub.i z.sub.i.sup.2
in which c is the molal concentration of a particular ionic species and z the absolute value of its charge. The sum .SIGMA. is taken over all the different kinds of ions (i) in solution.
U.S. Pat. No. 3,449,080 discusses measuring dissolved sodium or chloride ions. It is directed to a test device for determining the concentrations of these ions in body sweat. Briefly, there is disclosed in this patent the use of ion exchange resins together with a pH indicator. Using this device, the presence of sodium or chloride ions is said to be determined through a color change resulting from interaction between the ion exchange resin and the pH indicator. Whereas this reference purports to disclose a way of measuring ionic strength, it was found by the present inventors that such teachings, as set forth in the examples, were inapplicable to the measurement of specific gravity.
Both the osmolality and ionic strength approaches to indirectly determining specific gravity could conceivably be affected insofar as accuracy is concerned by the presence of nonionic species. Accordingly, U.S. Pat. No. 4,108,727, assigned to the present assignee, is directed to a method for removing this potential source of inaccuracy, and discloses a device in which the specific gravity-sensitive system contains an ionizing agent capable of converting the non-ionic solute to ionized species.
Finally, U.S. patent application No. 958,630, filed Nov. 8, 1978, and assigned to the present assignee, describes a device for using ionic strength for measuring specific gravity. This device utilizes a partially neutralized weak polyelectrolyte in the presence of a pH indicator. The present invention, on the other hand, represents a new approach whereby different polyelectrolytes having different properties are used.
To summarize the present state of the art as it might pertain to the present invention, many methods are known for the measurement of specific gravity, both direct and indirect. Direct measurement includes utilizing devices which are fragile, bulky and expensive, and which must be constantly cleaned, maintained and calibrated. Of the indirect methods, the measurement of the colligative solution property known as osmolality can provide an accurate correlation to specific gravity. The present invention utilizes a different perspective, the relationship between specific gravity and the ionic strength of a solution, and provides a device, composition and method for taking advantage of this relationship. As indicated above, U.S. Pat. No. 3,449,080 describes a method of gauging the concentration of sodium and/or chloride ions in body sweat. This patent utilizes the affinity of weakly acidic or weakly basic ion exchange resins for the unknown ions, and the color changing capacity of known pH indicators. None of the prior art known to the present inventors at the time of filing of the instant application teaches or suggests the invention presently disclosed and claimed.